Valtorcitabine Dihydrochloride

Conventional treatment of chronic hepatitis B with interferon alfa-2b, lamivudine, and adefovir is limited by low rates of sustained hepatitis B virus DNA suppression and hepatitis B e antigen (HBeAg) seroconversion, increasing rates of drug resistance to the oral agents, and poor tolerability of interferon. Recently several promising new antiviral agents have emerged that possess potent antiviral effects, less toxicity, and have little or no risk of drug resistance. Two new agents, entecavir and peginterferon alfa-2a, have received recent approval by regulatory authorities in the United States and several other countries for the treatment of adults with chronic hepatitis B. In large phase III clinical trials, these agents have demonstrated superior efficacy over lamivudine in both HBeAg-positive and HBeAg-negative patients. Drug resistance occurs at a low rate in lamivudine-refractory patients treated with entecavir or is, to date, nonexistent in nucleoside-naïve patients treated with entecavir and all patients receiving peginterferon. In addition, several novel agents in clinical development, such as emtricitabine, clevudine, telbivudine, valtorcitabine, and tenofovir, have shown promising clinical profiles in patients with chronic hepatitis B. This review summarizes the recent clinical studies of these new agents and discusses the implications of these data for the management of chronic hepatitis B.

Currently approved treatments for chronic infection with hepatitis B virus (HBV) are limited by low rates of sustained response, side effects, and in some cases, the emergence of drug resistance. Thus, new treatments, characterized by more potent antiviral effects less toxicity, and minimal or no risk of resistance, are needed. During the last few years, several agents have been developed that have increased potency and reduced potential for resistance--among them, entecavir and pegylated interferons. In addition, several novel anti-HBV agents recently evaluated in phase II clinical trials, such as tenofovir, clevudine, telbivudine, pradefovir, and valtorcitabine, appear to be promising agents for the treatment of chronic hepatitis B. This article describes the clinical experience with new antiviral agents and the implications of the trial results for practice guidelines.